Steve Sidney

Midlife cardiovascular risk factors and risk of dementia in late life

Objective: To evaluate if midlife cardiovascular risk factors are associated with risk of late-life dementia in a large, diverse cohort. Method: The authors conducted a retrospective cohort study of 8,845 participants of a health maintenance organization who underwent health evaluations from 1964 to 1973 when they were between the ages of 40 and 44. Midlife cardiovascular risk factors included total cholesterol, diabetes, hypertension, and smoking. Diagnoses of dementia were ascertained by medical records from January 1994 to April 2003. Results: The authors identified 721 participants (8.2%) with dementia. Smoking, hypertension, high cholesterol, and diabetes at midlife were each associated with a 20 to 40% increase in risk of dementia (fully adjusted Cox proportional hazards model: HR 1.24, 95% CI 1.04 to 1.48 for hypertension, HR 1.26, 95% CI 1.08 to 1.47 for smoking, HR 1.42, 95% CI 1.22 to 1.66 for high cholesterol, and HR 1.46, 95% CI 1.19 to 1.79 for diabetes). A composite cardiovascular risk score was created using all four risk factors and was associated with dementia in a dose-dependent fashion. Compared with participants having no risk factors, the risk for dementia increased from 1.27 for having one risk factor to 2.37 for having all four risk factors (fully adjusted model: HR 2.37, 95% CI 1.10 to 5.10). Conclusion: The presence of multiple cardiovascular risk factors at midlife substantially increases risk of late-life dementia in a dose dependent manner.

Socioeconomic status, race, and diurnal cortisol decline in the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Objectives: The objectives of this study were to assess whether socioeconomic status (SES) is associated with dysregulation of the cortisol diurnal rhythm and whether this association is independent of race and occurs equally in whites and blacks; and to determine if an association between SES and cortisol can be explained (is mediated) by behavioral, social, and emotional differences across the SES gradient. Methods: Seven hundred eighty-one subjects from a multisite sample representing both whites and blacks provided six saliva cortisol samples over the course of the day: at awakening, 45 minutes, 2.5 hours, 8 hours, and 12 hours after awakening, and at bedtime. Results: Both lower SES (education and income) and being black were associated with higher evening levels of cortisol. These relationships were independent of one another and SES associations with cortisol were similar across racial categories. The evidence was consistent with poorer health practices (primarily smoking), higher levels of depressive symptoms, poorer social networks and supports, and feelings of helplessness (low mastery) mediating the link between SES and cortisol. However, we found no evidence for psychosocial or behavioral mediation of the association between race and cortisol response. Conclusions: Lower SES was associated in a graded fashion with flatter diurnal rhythms as a result of less of a decline during the evening. This association occurred independent of race and the data were consistent with mediation by health practices, emotional and social factors. Blacks also showed a flatter rhythm at the end of the day. This association was independent of SES and could not be explained by behavioral, social, or emotional mediators. CARDIA = Coronary Artery Risk Development in Young Adults Study; SES = socioeconomic status; HPA = hypothalamic–pituitary adrenocortical; BMI = body mass index; AUC = area under the curve; CES-D = Center for Epidemiologic Studies Depression scale; MIDUS = Midlife in the U.S. Survey; PAH = Physical Activities History questionnaire.

Short sleep duration and incident coronary artery calcification

CONTEXT Coronary artery calcification is a subclinical predictor of coronary heart disease. Recent studies have found that sleep duration is correlated with established risk factors for calcification including glucose regulation, blood pressure, sex, age, education, and body mass index. OBJECTIVE To determine whether objective and subjective measures of sleep duration and quality are associated with incidence of calcification over 5 years and whether calcification risk factors mediate the association. DESIGN, SETTING, AND PARTICIPANTS Observational cohort of home monitoring in a healthy middle-aged population of 495 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort Chicago site (black and white men and women aged 35-47 years at year 15 of the study in 2000-2001 with follow-up data at year 20 in 2005-2006). Potential confounders (age, sex, race, education, apnea risk, smoking status) and mediators (lipids, blood pressure, body mass index, diabetes, inflammatory markers, alcohol consumption, depression, hostility, self-reported medical conditions) were measured at both baseline and follow-up. Sleep metrics (wrist actigraphy measured duration and fragmentation, daytime sleepiness, overall quality, self-reported duration) were examined for association with incident calcification. Participants had no detectable calcification at baseline. MAIN OUTCOME MEASURE Coronary artery calcification was measured by computed tomography in 2000-2001 and 2005-2006 and incidence of new calcification over that time was the primary outcome. RESULTS Five-year calcification incidence was 12.3% (n = 61). Longer measured sleep duration was significantly associated with reduced calcification incidence (adjusted odds ratio, 0.67 per hour [95% confidence interval, 0.49-0.91 per hour]; P = .01). No potential mediators appreciably altered the magnitude or significance of sleep (adjusted odds ratio estimates ranged from 0.64 to 0.68 per sleep hour; maximum P = .02). Alternative sleep metrics were not significantly associated with calcification. CONCLUSION Longer measured sleep is associated with lower calcification incidence independent of examined potential mediators and confounders.

Active commuting and cardiovascular disease risk: the CARDIA study.

BACKGROUND There is little research on the association of lifestyle exercise, such as active commuting (walking or biking to work), with obesity, fitness, and cardiovascular disease (CVD) risk factors. METHODS This cross-sectional study included 2364 participants enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study who worked outside the home during year 20 of the study (2005-2006). Associations between walking or biking to work (self-reported time, distance, and mode of commuting) with body weight (measured height and weight); obesity (body mass index [BMI], calculated as weight in kilograms divided by height in meters squared, >or= 30); fitness (symptom-limited exercise stress testing); objective moderate-vigorous physical activity (accelerometry); CVD risk factors (blood pressure [oscillometric systolic and diastolic]); and serum measures (fasting measures of lipid, glucose, and insulin levels) were separately assessed by sex-stratified multivariable linear (or logistic) regression modeling. RESULTS A total of 16.7% of participants used any means of active commuting to work. Controlling for age, race, income, education, smoking, examination center, and physical activity index excluding walking, men with any active commuting (vs none) had reduced likelihood of obesity (odds ratio [OR], 0.50; 95% confidence interval [CI], 0.33-0.76), reduced CVD risk: ratio of geometric mean triglyceride levels (trig(active))/(trig(nonactive)) = 0.88 (95% CI, 0.80 to 0.98); ratio of geometric mean fasting insulin (FI(active))/(FI(nonactive)) = 0.86 (95% CI, 0.78 to 0.93); difference in mean diastolic blood pressure (millimeters of mercury) (DBP(active)) - (DBP(nonactive)) = -1.67 (95% CI, -3.20 to -0.15); and higher fitness: mean difference in treadmill test duration (in seconds) in men (TT(active)) - (TT(nonactive)) = 50.0 (95% CI, 31.45 to 68.59) and women (TT(active)) - (TT(nonactive)) = 28.77 (95% CI, 11.61 to 45.92). CONCLUSIONS Active commuting was positively associated with fitness in men and women and inversely associated with BMI, obesity, triglyceride levels, blood pressure, and insulin level in men. Active commuting should be investigated as a modality for maintaining or improving health.

Excess gains in weight and waist circumference associated with childbearing: The Coronary Artery Risk Development in Young Adults Study (CARDIA)

OBJECTIVE: To examine the association of childbearing with weight and waist circumference (WC) changes, we compared women with and without pregnancies or births during follow-up.STUDY DESIGN: A multicenter, longitudinal observational study over 10 years. Comparison groups defined by the number of pregnancies and births during follow-up: P0 (0 pregnancies; nongravid), P1 (1+ miscarriages or abortions; ‘short’ pregnancies), B1 (1 birth), and B2 (2+ births). Mean changes in weight and WC for P1, B1 and B2 groups vs P0 were examined separately by race (black and white), baseline parity (nulliparous and parous) and baseline weight status (normal weight; BMI <25 kg/m2 and overweight; BMI ≥25 kg/m2).SUBJECTS: A population-based sample of 2070 women aged 18–30 y at baseline (1053 black subjects and 1017 white subjects) from Birmingham, Alabama, Chicago, Illinois, Minneapolis, Minnesota, and Oakland, California were examined five times between 1985–1986 and 1995–1996.MEASURMENTS: Weight and WC measurements were obtained using standardized protocol at baseline and examinations at years 2, 5, 7 and 10. Sociodemographic, reproductive, and behavioral attributes were assessed at baseline and follow-up examinations.RESULTS: Gains in weight and WC associated with pregnancy and childbearing varied by race (P<0.001), baseline parity (P<0.05) and overweight status (P<0.001). Among overweight nulliparas, excess gains in weight (black subjects: 3–5 kg, white subjects: 5–6 kg) and WC (black subjects: 3–4 cm, white subjects: 5–6 cm) were associated with ‘short’ pregnancies and one or more birth(s) during follow-up compared to no pregnancies (P<0.01 and 0.001). Among normal weight nulliparas, excess gains in weight (about 1 kg) and WC (2–3 cm) were associated with follow-up birth(s) (P<0.05). Among women parous at baseline, no excess weight gains were found, but excess WC gains (2–4 cm) were associated with follow-up births.CONCLUSION: Substantial excess weight gain is associated with both short pregnancies and a first birth in women overweight prior to initiation of childbearing. Excess weight gain was not associated with higher order births. Increases in waist girth were cumulative with both first and higher order births among overweight as well as normal weight women. Interventions to prevent obesity should be targeted at women who are overweight prior to initiation of childbearing. The impact of excess WC gains associated with childbearing on womens future health risk should be evaluated further.

Prehypertension during Young Adulthood and Coronary Calcium Later in Life

Context The long-term effects of prehypertension in young adults are not well defined. Contribution These investigators found that young adults with systolic prehypertension were more likely than those without prehypertension to have coronary artery calcium. Caution Not all patients with coronary artery calcium develop clinically significant cardiovascular disease. Implication Prehypertension in young adulthood is associated with coronary artery calcium in middle age. The Editors High blood pressure in middle-age and older populations is a strong risk factor for cardiovascular disease (1). Among adults age 40 years or older, each 20mm Hg increase in systolic blood pressure is associated with an approximate doubling in the short-term risk (within 5 years) of a cardiovascular disease event (2, 3). Clinical trials show that lowering blood pressure with antihypertensive medications reduces this short-term risk (4), but damage from blood pressure elevation seems to accumulate over time, such that damage from past exposure may not be completely reversible with treatment later in life. Cohort studies in elderly persons show that blood pressure elevation even 20 to 30 years in the past is associated with cardiovascular events (5, 6) and atherosclerosis (7) independent of current blood pressure. Less is known about the effects of blood pressure elevation during young adulthood. Although hypertension (systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg) is rare before age 40 years, prehypertension (systolic blood pressure of 120 to 139 mm Hg, or diastolic blood pressure of 80 to 89 mm Hg [1]) is more common (8, 9). Current guidelines recommend lifestyle modification without pharmacotherapy for persons with prehypertension to reduce the risk for hypertension (1, 10), but whether prehypertension during young adulthood may itself cause vascular damage that persists later in life is unclear. In practice, suboptimal blood pressure that remains below 140/90 mm Hg are often ignored in young adults (8). The CARDIA (Coronary Artery Risk Development in Young Adults) Study provides a unique opportunity to evaluate the consequences of prehypertension during young adulthood. Using CARDIAs repeated measures of blood pressure starting at the outset of adulthood and continuing over 20 years of follow-up, we identified participants exposed to prehypertension between age 20 and 35 years, estimated cumulative exposure in mm Hgyears (similar to pack-years of tobacco exposure), and observed associations with coronary calcium levels measured later in life. Methods Study Design and Sample Population The CARDIA Study is a longitudinal cohort of 5115 black and white women and men recruited in 1985 from 4 U.S. cities. The participants were 18 to 30 years old and healthy at enrollment (11, 12). The participants underwent a baseline examination and follow-up examinations at years 2, 5, 7, 10, 15, and 20. For our investigation, we identified all CARDIA participants who had cardiac computed tomography for coronary calcium in either the 15-year or 20-year follow-up examination and excluded participants who developed hypertension (systolic blood pressure 140 mm Hg, diastolic blood pressure 90 mm Hg, or taking a blood pressure medication) before the age of 35 years. Blood Pressure At each CARDIA examination, research staff measured right-arm blood pressure 3 times after the participant had been sitting in a quiet room for 5 minutes. We used the average of the second and third readings. Members of the CARDIA research staff took measurements by using a Hawksley random-zero sphygmomanometer (Hawksley, Sussex, United Kingdom) until the last examination at year 20, when concerns about mercury contained in the apparatus required a switch to the OmROn HEM907XL sphygmomanometer (Omron Corporation, Kyoto, Japan). Dual measurement on a subgroup of participants was used to calibrate the new measurements and assure comparability. Estimating Systolic Blood Pressure Trajectories and Cumulative Exposure We used mixed models to estimate a blood pressure trajectory (systolic and diastolic) for each participant from age 20 years up to the time of his or her coronary calcium measurement. We assumed that the trajectory for each participant had a constant slope within each decade of life (age 20 to 30 years, 30 to 40 years, and 40 to 50 years), so we allowed each participant a different random intercept and 3 random slopes, modeled as deviations from race- and sex-specific mean trajectories. (See the Appendix for details.) Using these individual blood pressure trajectories, we then calculated an integrated, cumulative measure of years of exposure to blood pressure elevation for each participant, measured in mm Hgyears, by calculating the area under the trajectory for each participant in the blood pressure range of interest. We considered the area under the blood pressure trajectory before the age of 35 years and in the prehypertension range (systolic blood pressure of 120 to 139 mm Hg, or diastolic blood pressure of 80 to 89 mm Hg) to be the primary predictor for this analysis and referred to this measurement as the cumulative exposure to prehypertension during young adulthood. We used the area under the blood pressure trajectory after age 35 years as a covariate in the multivariable analysis. Coronary Calcium Consenting CARDIA participants had cardiac computed tomography, with an electron-beam or multidetector electrocardiographically gated cardiac computed tomography scanner, at year 15 and year 20 to measure coronary calcium level, which represents calcified plaque in the coronary arteries (13, 14). Technicians obtained 2 sequential coronary calcium scans by using a standard phantom with known concentrations of calcium hydroxyapatite for calibration and performed imaging by using prospective gating in late diastole, a slice thickness of 2.5 to 3.0 mm, a reconstruction into a 35-cm field of view, and a temporal resolution of 100 to 520 ms (year 15 examination) and 100 to 250 ms (year 20 examination). Experienced image analysts who were blinded to participant information and the paired scan identified calcified plaque in the epicardial coronary arteries and calculated a total coronary calcium score by using a modified Agatston method to account for slice thickness (15), a minimum lesion size of 4 adjacent pixels (an area 1.87 mm2), and a density greater than 130 Hounsfield units. An expert physician in cardiovascular imaging reviewed all scans that were discordant (1 with and 1 without coronary calcium), had a score greater than 200, had a change in calcium status between year 15 and year 20, had a possible surgical intervention (pacemaker, valve replacement, coronary stent, or bypass surgery), or had a concern identified by the reviewer. Other articles describe the accuracy, comparability, reproducibility, and robustness of calcium score measurement by using these methods (16, 17). For this analysis, we used the last nonmissing coronary calcium measurement (that is, the scan from year 20 if available; otherwise, the scan from year 15). Other Measurements Research staff obtained information on sex, race (black or white), date of birth, serum cotinine levels, and family history of premature coronary heart disease (defined by a mother or father with myocardial infarction before age 60 years) at baseline. We used levels of fasting plasma glucose (and diabetes status), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, and triglycerides, as well as smoking habits, from all CARDIA examinations. We took other covariates, including educational grade attained and income (self-reported), body mass index and waist circumference (directly measured), and physical activity (self-reported on a scale of 1 to 5) from the time of the coronary calcium scan (18). We estimated the cumulative exposure to LDL and HDL cholesterol, triglycerides, and fasting glucose (without partition by age or level) by the same method used for blood pressure. Statistical Analysis We described persons with and without prehypertension (systolic or diastolic) before age 35 years and compared characteristics by using t tests (for continuous variables) and chi-square tests (for dichotomous variables). To estimate independent cross-sectional associations of various demographic factors with prehypertension before age 35 years, we constructed a multivariable logistic regression model, regressing prehypertension before age 35 years on age, sex, and all incomeeducation combinations (3 education and 4 income categories for a total of 12 combined incomeeducation categories). Cumulative blood pressure exposure variables, including the primary predictor, were right-skewed with most participants having zero exposure, and the relationships between these continuous cumulative exposure measures and coronary calcium prevalence were closer to linear after log transformation of the cumulative exposure measure (adding 1 mm Hgyear before the log-transformation). Therefore, we presented our main adjusted results by using these log-transformed cumulative exposure measures as continuous predictors. Results are also presented by using categorized cumulative exposure measures. We calculated trends across categories and trend interactions by using adjusted Wald tests of linear combinations of regression coefficients. We used logistic regression to analyze the association between blood pressure elevation and the presence or absence of coronary calcium. We first analyzed the association of coronary calcium with categories of systolic and diastolic prehypertension, with simple adjustment or stratification for age, sex, race, and current blood pressure. We then fit models for our primary predictor (cumulative exposure to prehypertension before age 35 years), adjusting for a priorispecified potential confounders modeled flexibly with spline knots where suggested by linearity plots. These includ

Body composition and functional limitation in COPD.

BackgroundLow body mass index has been associated with increased mortality in severe COPD. The impact of body composition earlier in the disease remains unclear. We studied the impact of body composition on the risk of functional limitation in COPD.MethodsWe used bioelectrical impedance to estimate body composition in a cohort of 355 younger adults with COPD who had a broad spectrum of severity.ResultsAmong women, a higher lean-to-fat ratio was associated with a lower risk of self-reported functional limitation after controlling for age, height, pulmonary function impairment, race, education, and smoking history (OR 0.45 per 0.50 increment in lean-to-fat ratio; 95% CI 0.28 to 0.74). Among men, a higher lean-to-fat ratio was associated with a greater distance walked in 6 minutes (mean difference 40 meters per 0.50 ratio increment; 95% CI 9 to 71 meters). In women, the lean-to-fat ratio was associated with an even greater distance walked (mean difference 162 meters per 0.50 increment; 95% CI 97 to 228 meters). In women, higher lean-to-fat ratio was also associated with better Short Physical Performance Battery Scores. In further analysis, the accumulation of greater fat mass, and not the loss of lean mass, was most strongly associated with functional limitation among both sexes.ConclusionBody composition is an important non-pulmonary impairment that modulates the risk of functional limitation in COPD, even after taking pulmonary function into account. Body composition abnormalities may represent an important area for screening and preventive intervention in COPD.

Modeling multisystem biological risk in young adults: The Coronary Artery Risk Development in Young Adults Study

Although much prior research has focused on identifying the roles of major regulatory systems in health risks, the concept of allostatic load (AL) focuses on the importance of a more multisystems view of health risks. How best to operationalize allostatic load, however, remains the subject of some debate. We sought to test a hypothesized metafactor model of allostatic load composed of a number of biological system factors, and to investigate model invariance across sex and ethnicity. Biological data from 782 men and women, aged 32–47, from the Oakland, CA and Chicago, IL sites of the Coronary Artery Risk Development in Young Adults Study (CARDIA) were collected as part of the Year 15exam in 2000. These include measures of blood pressure, metabolic parameters (glucose, insulin, lipid profiles, and waist circumference), markers of inflammation (interleukin‐6, C‐reactive protein, and fibrinogen), heart rate variability, sympathetic nervous system activity (12‐hr urinary norepinephrine and epinephrine) and hypothalamic‐pituitary‐adrenal axis activity (diurnal salivary free cortisol). A “metafactor” model of AL as an aggregate measure of six underlying latent biological subfactors was found to fit the data, with the metafactor structure capturing 84% of variance of all pairwise associations among biological subsystems. There was little evidence of model variance across sex and/or ethnicity. These analyses extend work operationalizing AL as a multisystems index of biological dysregulation, providing initial support for a model of AL as a metaconstruct of inter‐relationships among multiple biological regulatory systems, that varies little across sex or ethnicity. Am. J. Hum. Biol. 2010.

A comparison of risk factors for recurrent TIA and stroke in patients diagnosed with TIA

Background: Some spells consistent with TIA may be benign, such as those produced by migraine or migraine accompaniments in the elderly. Distinguishing these from embolic or thrombotic events may be difficult. Methods: Emergency department physicians identified patients who presented with a presumed TIA at one of 16 hospitals in Northern California from March 1997 through February 1998. Recurrent TIAs and strokes were recorded for 90 days afterwards. Results: Of 1,707 patients in whom TIA had been diagnosed in the emergency department, 191 (11.2%) had a recurrent TIA and 180 (10.5%) had a stroke during 90-day followup. Independent risk factors for recurrent TIA were age >60 years (odds ratio 1.9; 95% CI 1.2 to 2.9; p = 0.003), history of multiple TIAs (odds ratio 2.9; 2.1 to 4.0; p < 0.001), duration of spell ≤10 minutes (odds ratio 2.3; 1.6 to 3.3; p < 0.001), and sensory abnormality associated with the spell (odds ratio 1.9; 1.4 to 2.6; p < 0.001). Independent risk factors for stroke from a previous analysis were age, duration >10 minutes, diabetes, weakness, and speech impairment. Among the 30 patients with isolated sensory symptoms lasting ≤10 minutes, the risk of recurrent TIA was 40% and none had a stroke. Conclusions: In patients in whom TIA has been diagnosed in the emergency department, risk factors for subsequent stroke and recurrent TIA are different. A subset of patients with presumed TIA has a benign short-term course with multiple brief TIAs more frequently characterized by sensory symptoms.

Lactation and Changes in Maternal Metabolic Risk Factors

OBJECTIVE: To examine the relationship between duration of lactation and changes in maternal metabolic risk factors. METHODS: This 3-year prospective study examined changes in metabolic risk factors among lactating women from preconception to postweaning and among nonlactating women from preconception to postdelivery, in comparison with nongravid women. Of 1,051 (490 black, 561 white) women who attended two consecutive study visits in years 7 (1992–1993) and 10 (1995–1996), 942 were nongravid and 109 had one interim birth. Of parous women, 48 (45%) did not lactate, and 61 (55%) lactated and weaned before year 10. The lactated and weaned women were subdivided by duration of lactation into less than 3 months and 3 months or more. Multiple linear regression models estimated mean 3-year changes in metabolic risk factors adjusted for age, race, parity, education, and behavioral covariates. RESULTS: Both parous women who did not lactate and parous women who lactated and weaned gained more weight (+5.6, +4.4 kg) and waist girth (+5.3, +4.9 cm) than nongravid women over the 3-year interval; P<.001. Low-density lipoprotein cholesterol (+6.7 mg/dL, P<.05) and fasting insulin (+2.6 microunits, P=.06) increased more for parous women who did not lactate than for nongravid and parous women who lactated and weaned. High-density lipoprotein cholesterol decrements for both parous women who did not lactate and parous women who lactated and weaned were 4.0 mg/dL greater than for nongravid women (P<.001). Among parous, lactated and weaned women, lactation for 3 months or longer was associated with a smaller decrement in high-density lipoprotein cholesterol (–1.3 mg/dL versus –7.3 mg/dL for less than 3 months; P<.01). CONCLUSION: Lactation may attenuate unfavorable metabolic risk factor changes that occur with pregnancy, with effects apparent after weaning. As a modifiable behavior, lactation may affect womens future risk of cardiovascular and metabolic diseases. LEVEL OF EVIDENCE: II